Prediction by uterine artery Doppler screening of small-for-gestational-age neonates at 19-24 weeks' gestation.

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

'Nausicaa' compression suture: a simple and effective alternative to hysterectomy in placenta accreta spectrum and other causes of severe postpartum haemorrhage.

Postpartum haemorrhage (PPH), especially resulting from placenta accreta spectrum (PAS), has become a worldwide concern in maternity care. We describe a novel method of uterine compression sutures (the 'Nausicaa' technique) as an alternative to hysterectomy for patients who have suffered from major PPH. We applied this technique in 68 patients with major PPH during caesarean section (including 43 patients with PAS, 20 patients with placenta praevia totalis, and five patients with uterine atony), and none of these patients required further hysterectomy. We conclude that our Nausicaa suture is a simple and feasible alternative to hysterectomy in patients suffering from major PPH.

Full Electroresistance Modulation in a Mixed-Phase Metallic Alloy.

We report a giant, ∼22%, electroresistance modulation for a metallic alloy above room temperature. It is achieved by a small electric field of 2 kV/cm via piezoelectric strain-mediated magnetoelectric coupling and the resulting magnetic phase transition in epitaxial FeRh/BaTiO_{3} heterostructures. This work presents detailed experimental evidence for an isothermal magnetic phase transition driven by tetragonality modulation in FeRh thin films, which is in contrast to the large volume expansion in the conventional temperature-driven magnetic phase transition in FeRh. Moreover, all the experimental results in this work illustrate FeRh as a mixed-phase model system well similar to phase-separated colossal magnetoresistance systems with phase instability therein.

Betulinic acid enhances TGF-ß signaling by altering TGF-ß receptors partitioning between lipid-raft/caveolae and non-caveolae membrane microdomains in mink lung epithelial cells.

BACKGROUND: TGF-ß is a key modulator in the regulation of cell proliferation and migration, and is also involved in the process of cancer development and progression. Previous studies have indicated that TGF-ß responsiveness is determined by TGF-ß receptor partitioning between lipid raft/caveolae-mediated and clathrin-mediated endocytosis. Lipid raft/caveolae-mediated endocytosis facilitates TGF-ß degradation and thus suppressing TGF-ß responsiveness. By contrast, clathrin-mediated endocytosis results in Smad2/3-dependent endosomal signaling, thereby promoting TGF-ß responsiveness. Because betulinic acid shares a similar chemical structure with cholesterol and has been reported to insert into the plasma membrane, we speculate that betulinic acid changes the fluidity of the plasma membrane and modulates the signaling pathway associated with membrane microdomains. We propose that betulinic acid modulates TGF-ß responsiveness by changing the partitioning of TGF-ß receptor between lipid-raft/caveolae and non-caveolae microdomain on plasma membrane. METHODS: We employed sucrose-density gradient ultracentrifugation and confocal microscopy to determine membrane localization of TGF-ß receptors and used a luciferase assay to examine the effects of betulinic acid in TGF-ß-stimulated promoter activation. In addition, we perform western blotting to test TGF-ß-induced Smad2 phosphorylation and fibronectin production. RESULTS AND CONCLUSIONS: Betulinic acid induces translocation of TGF-ß receptors from lipid raft/caveolae to non-caveolae microdomains without changing total level of TGF-ß receptors. The betulinic acid-induced TGF-ß receptors translocation is rapid and correlate with the TGF-ß-induced PAI-1 reporter gene activation and growth inhibition in Mv1Lu cells.

Treatment outcomes in a cohort of patients with mucosal-predominant pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a rare autoimmune blistering condition. Treatment typically combines corticosteroids with another immunosuppressive agent, such as azathioprine, mycophenolate mofetil (MMF) or rituximab. AIM: This study aims to compare these second agents for their clinical efficacy and steroid-sparing effect. METHODS: This was a single-centre, retrospective observational cohort study of 21 patients with oral PV over a 6-year period, 18 of whom were newly diagnosed. Of the latter, the first 13 were initially given azathioprine, progressing to MMF and then rituximab on treatment failure, while the next five patients started directly on MMF. RESULTS: Of the 13 newly diagnosed patients, 2/13 were intolerant of azathioprine, and only 1/11 was controlled, with a median time to treatment failure (MTTF) of 254 days. MMF was given to 17 patients, either de novo (5) or after azathioprine (12), and was significantly more effective, controlling activity in 4/17 patients, and for a significantly longer time (MTTF 395 days, P = 0.019). All 13 patients failing MMF received rituximab, seven required a second dose, and three, a third dose. All patients responded, with 11/13 able to cease steroids. Control was maintained for a similar time to MMF (MTTF 364 days, P = NS). Rituximab also had the best steroid-sparing effect followed by MMF, then azathioprine. Side-effects were common with azathioprine, while the other two agents were well tolerated. CONCLUSION: Rituximab was the most effective of the three immunosuppressives for PV, although repeat dosing was frequently required. These observations have significant implications for the choice of drugs for this condition.

Comorbidity profiles in association with vitiligo: a nationwide population-based study in Taiwan.

BACKGROUND: The previous literature has demonstrated the association of autoimmune and atopic diseases with vitiligo, but there has been no large-scale nationwide study conducted to confirm this. OBJECTIVES: The present study was conducted to clarify the comorbid profiles in vitiligo patients and thereby better understand their clinical scenarios and underlying pathogenesis. METHODS: This was a retrospective population-based study conducted from 1996 to 2011 via the National Health Insurance Research Database in Taiwan. The differences in the prevalence of multiple autoimmune and atopic diseases between case subjects and controls were analysed by multiple logistic regression method. RESULTS: A total of 14883 vitiligo patients and 59532 controls were enroled. The prevalence of vitiligo was 0.064% and the peak of onset age was 40-59 years old. The non-stratified analysis evidenced a significant association between vitiligo and several comorbid diseases, including alopecia areata, Hashimoto thyroiditis, myasthenia gravis, psoriasis, Graves' disease, Sjögren's syndrome, systemic lupus erythematosus and atopic dermatitis. Vitiligo patients also had higher prevalence of multiple comorbidities than controls. In the age- and gender-stratified analysis, increased risks of systemic lupus erythematosus and Sjögren's syndrome were observed only in subjects aged 60-79. The association of vitiligo with myasthenia gravis and rheumatoid arthritis was identified only in the subgroup aged 20-39 and in females aged 60-79 respectively. CONCLUSION: Our study not only confirmed the significant association of vitiligo with multiple autoimmune and atopic diseases in Taiwan but also disclosed several unique findings, including the much lower prevalence of vitiligo, delayed onset of vitiligo by three decades, different associated comorbidity profiles comparing to westerners and the age- and gender-specific approach for the vitiligo-associated comorbidities.

Autoimmune comorbid diseases associated with lichen planus: a nationwide case-control study.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory disorder with unknown aetiology. The association between LP and various autoimmune diseases has been reported, but nationwide study of the relationship of LP with associated diseases is quite limited. OBJECTIVE: Our study aims to clarify the association between LP and a variety of autoimmune diseases in Taiwanese. METHODS: Data were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan from 1997 to 2011. In total, 12,427 patients with LP and 49,708 age- and gender-matched controls were enrolled. RESULTS: Among patients with LP, there were significant associations with systemic lupus erythematosus (SLE) (multivariate odds ratio [mOR]: 2.87; 95% CI: 1.97-4.17), Sjögren's syndrome (mOR: 3.75; 95% CI: 2.66-5.28), dermatomyositis (mOR: 6.34; 95% CI: 1.82-22.16), vitiligo (mOR: 2.09; 95% CI: 1.31-3.32) and alopecia areata (mOR: 2.82; 95% CI: 2.20-3.62). On gender-stratified analyses, SLE and alopecia areata were significantly associated with LP in both genders. The association with Sjögren's syndrome was significant only in female patients. The associations with dermatomyositis and vitiligo became insignificant in both genders. CONCLUSION: Lichen planus is associated with various autoimmune diseases. Further study is required to elucidate the possible underlying mechanisms and roles of autoimmunity in the aetiology of LP.

Vancomycin-associated drug reaction with eosinophilia and systemic symptoms syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially life-threatening multi-system disorder characterised by the delayed onset of fever, rash and internal organ involvement following the administration of a drug. We report three definite cases of vancomycin-associated DRESS syndrome occurring and review the literature regarding this syndrome.

Extra-pancreatic manifestations of IgG4-related systemic disease: a single-centre experience of treatment with combined immunosuppression.

BACKGROUND/AIM: IgG4-related systemic disease (IgG4-RSD) is a systemic inflammatory disease distinguished by tissue infiltrates of IgG4(+) plasma cells and elevated serum IgG4 levels. While IgG4-RSD often involves the pancreas, extra-pancreatic organs are also frequently affected. Here, we review the presentation and management of patients with extra-pancreatic IgG4-RSD. METHODS: A retrospective analysis was performed on patients diagnosed with extra-pancreatic IgG4-RSD identified from a single centre. RESULTS: Six patients with extra-pancreatic IgG4-RSD were identified. The median age of the patients was 64 years. The range of involved organs included lymph nodes (three patients), ocular adnexa, lung, kidneys, meninges and exocrine glands. The median delay in diagnosis was 13.5 months (4-60 months). Four patients had elevated serum IgG4 levels at diagnosis. Five symptomatic patients were commenced on combination immunosuppression, which included corticosteroids. Maintenance therapy with azathioprine was used in one patient, methotrexate and mycophenolate were each used in two patients, and cyclophosphamide in one patient. Four treated patients went into remission, while two patients had persistent radiological disease. One patient experienced two relapses. CONCLUSION: IgG4-RSD can manifest in a variety of organs. Lack of awareness regarding this entity may delay diagnosis. Combination treatment of corticosteroids and conventional immunosuppression is effective.

[A retrospective cohort study of case fatality rate of HIV/AIDS cases and influencing factors in Jingzhou, Hubei Province, 1996-2021].

Objective: To analyze the case fatality rate of HIV/AIDS cases and influencing factors in Jingzhou. Methods: The data were retrieved from HIV/AIDS Comprehensive Response Information System and the cases diagnosed with HIV/AIDS in Jingzhou during 1996-2021 and aged 15 years or older were selected for the study. The death curve was drawn with Kaplan-Meier method, and Cox proportional-hazards model was used to identify influencing factors for death. Results: A total of 3 304 HIV/AIDS cases were followed up for 16 091.5 person-years, and 893 cases died, with a case fatality rate of 5.5/100 person-years. The cumulative case fatality rates of 1, 5 and 10 years were 15.4%, 25.0% and 34.6% respectively, the cumulative case fatality rates of 1, 5 and 10 years were 6.9%, 14.4% and 23.7% in the cases with access to antiretroviral therapy (ART), and 68.0%, 90.1% and 98.7% in the cases without access to ART. The results of Cox proportional hazards regression model showed that the risk for death was higher in those without access to ART than in those with access to ART (aHR=9.85, 95%CI: 8.19-11.85). The risk factors for death in those with access to ART included being men (aHR=1.64, 95%CI: 1.29-2.08), age ≥60 years old at diagnosis (aHR=3.52, 95%CI: 2.38-5.20), being infected by injecting drug use/others (aHR=2.38, 95%CI:1.30-4.34), being detected by medical institution (aHR=1.53, 95%CI: 1.11-2.11), CD4+T lymphocytes(CD4) counts <50 cells/µl (aHR=2.58, 95%CI: 1.87-3.58). The protective factor for death was high education level (high school and technical secondary school: aHR=0.64,95%CI:0.46-0.90; college and above: aHR=0.42, 95%CI: 0.24-0.73). The risk factors for HIV/AIDS death in those without access to ART included older age at diagnosis (30-44 years old: aHR=2.32, 95%CI: 1.40-3.84; 45-59 years old:aHR=2.61, 95%CI: 1.59-4.27; ≥60 years old: aHR=3.31, 95%CI: 2.01-5.47), lower CD4 counts (<50 cells/µl: aHR=10.47, 95%CI: 6.47-16.56; 50-199 cells/µl: aHR=2.31, 95%CI: 1.08-4.94; 200-349 cells/µl: aHR=2.35, 95%CI: 1.46-3.79). Conclusions: The case fatality rate of HIV/AIDS was relatively high in Jingzhou from 1996 to 2021, the first CD4 counts, ART and age at diagnosis were the major factors affecting HIV/AIDS death, "Expanding testing" and "prompt treatment upon diagnosis" should be continued and enhanced to improve the efficacy of ART and HIV/AIDS case survival.

Psychiatric comorbidities in patients with alopecia areata in Taiwan: a case-control study.

BACKGROUND: Alopecia areata (AA) may be related to stress and has been reported to be associated with psychiatric disorders. Nevertheless, a nationwide study of the relationship between AA and comorbid psychiatric diseases has not been conducted, and the effect of onset age has rarely been reported. OBJECTIVES: To analyse the associations between AA and various psychiatric disorders using a nationwide database in Taiwan. METHODS: Data were obtained from the National Health Insurance Research Database of Taiwan from 2000 to 2009. In total, 5117 patients with AA and 20 468 age- and gender-matched controls were enrolled. RESULTS: Patients with AA tended to have more coexisting anxiety and less comorbid schizophrenia. Differences in ages of onset revealed differences in comorbidities. An increased risk of depression [odds ratio (OR) 2·23; 95% confidence interval (CI) 1·09-4·54] was found in patients with AA aged < 20years. An increased rate of anxiety (OR 1·43; CI 1·15-1·77) was observed with AA onset between the ages of 20 and 39years. The highest odds of obsessive-compulsive disorder (OR 3·00; CI 1·11-8·12) and anxiety (OR 2·05; CI 1·56-2·68) were observed in patients with AA aged 40-59years. Moreover, about 50% of psychiatric disorders occurred earlier than AA. CONCLUSIONS: AA is related to various psychiatric disorders. Onset age of AA is an important factor in the association with different comorbid psychiatric diseases. In addition to cosmetic impact, which may bring about anxiety or depression, stress neuroendocrine immunology may play an important role in the pathogenesis of both AA and psychiatric disorders.

Molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea.

OBJECTIVE: This study aimed to elucidate whether molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea. METHOD: Twenty patients with mild obstructive sleep apnoea (control group) and 40 patients with moderate to severe obstructive sleep apnoea (obstructive sleep apnoea group) who desired uvulopalatopharyngoplasty were recruited for the study. After uvulopalatopharyngoplasty, surgical specimens of the uvula were subjected to haematoxylin and eosin, Masson's trichrome and immunohistochemical staining. Western blot and reverse transcriptase-polymerase chain reaction were used to evaluate the protein and messenger RNA expressions. RESULTS: The obstructive sleep apnoea group showed more severe inflammation, increased collagen deposition and higher immunohistochemical staining intensity for TGF-ß and MMP-9 as well as higher protein and messenger RNA expression of MMP-9, VEGF, TGF-ß, p38 MAPK, SMAD 2/3, AKT and JNK in the uvula than control group. CONCLUSION: Patients with obstructive sleep apnoea demonstrated more severe inflammation, increased airway remodelling, and increased protein and messenger RNA expression of pro-inflammatory and pro-fibrotic cytokines in the uvula than control participants.

Comorbidity profiles among patients with bullous pemphigoid: a nationwide population-based study.

BACKGROUND: Bullous pemphigoid (BP) has been associated with neurological and psychiatric diseases; however, large-scale population-based study of different comorbid diseases in patients with BP is quite limited. OBJECTIVES: We sought to analyse the prevalence of neurological, psychiatric, autoimmune and inflammatory skin diseases prior to the diagnosis of BP and their associations with BP among patients with BP from a nationwide database in Taiwan. METHODS: A total of 3485 patients with BP and 17,425 matching controls were identified from the National Health Insurance Database in Taiwan from 1997 to 2008. Conditional logistic regression analyses for a nested case-control study were performed to examine the prevalence of comorbidities prior to the diagnosis of BP between these two groups. RESULTS: Overall, our results showed that stroke [odds ratio (OR) 3·30; 95% confidence interval (95% CI) 3·03-3·60], dementia (OR 4·81; 95% CI 4·26-5·42), Parkinson disease (OR 3·49; 95% CI 3·05-3·98), epilepsy (OR 3·97; 95% CI 3·28-4·81), schizophrenia (OR 2·56; 95% CI 1·52-4·30) and psoriasis (OR 2·02; 95% CI 1·54-2·66) were significantly associated with BP. Among them, the association with schizophrenia and psoriasis was predominant in female and male patients, respectively, with BP. It remains for all these comorbid diseases to be independently associated with BP by multivariate analysis. CONCLUSIONS: Patients with BP are more likely to have various neurological diseases, schizophrenia and psoriasis prior to the diagnosis of BP, supporting associations found in other studies. Further research is required to elucidate the tentative causal association with BP.

Carnitine and carnitine orotate affect the expression of the prolactin-releasing peptide gene.

Carnitine is involved in fatty acid metabolism in mammals and is widely used as a nutritional supplement; carnitine orotate is a more absorbable form of carnitine. We investigated the effects of carnitine and carnitine orotate on mouse prolactin-releasing peptide (PrRP) mRNA expression. Twenty-four female mice were randomly divided into four groups of six; control mice were orally drenched with physiological saline solution (250 mg/kg body weight) and treatment mice were orally drenched with carnitine (250 mg/kg) or carnitine orotate (250 or 750 mg/kg), once a day, for 20 days from parturition. The carnitine or carnitine orotate was dissolved in saline solution before administration. The hypothalamus, pituitary and ovary were sampled on day 21 after parturition, and PrRP mRNA levels in these tissues were measured by semi-quantitative PCR, with glyceraldehyde 3-phosphate dehydrogenase as a control. Expression of PrRP in mice treated with carnitine and carnitine orotate was significantly increased in the ovary and significantly reduced in the pituitary gland. Compared with the control, hypothalamus PrRP mRNA increased significantly in the carnitine and low-dose carnitine orotate groups and decreased significantly in the high-dose carnitine orotate group. We conclude that carnitine and carnitine orotate regulate expression of PrRP in the pituitary gland and ovaries.

Association of the G-protein and α2-adrenergic receptor gene and plasma norepinephrine level with clonidine improvement of the effects of diuretics in patients with cirrhosis with refractory ascites: a randomised clinical trial.

OBJECTIVE: Clonidine is an α(2)-adrenoceptor agonist which, by coupling with G-protein, has been proposed as an alternative treatment for refractory ascites of patients with cirrhosis for several years. Genetic polymorphisms of ß-adrenoceptor and angiotensin II type 1 receptor blockers have been reported to affect drug response in patients with cirrhosis. This study evaluated the clonidine-diuretic response rate, favourable predictors and genetic components of the clonidine-diuretic response in patients with cirrhosis with refractory ascites. METHODS: 270 patients with cirrhosis with refractory ascites were randomised equally into two treatment groups to receive diuretics alone or the clonidine-diuretics association. The primary end point was clonidine-diuretic response rate. Secondary end points were mean daily dose of diuretics, times of paracentesis, ascites-related readmission and 1-year survival rate. RESULTS: Good clonidine responders had better natriuresis and diuresis as well as a significant decrease in abdominal circumference, plasma renin, aldosterone and norepinephrine levels. The overall clonidine-diuretics response rate was 55-60%. In patients with cirrhosis, the prevalence of ARDA(2)C WD/DD and GNB3 CT/TT genotypes was 71% and 77%, respectively. Among the responders, 71% of patients with cirrhosis had the ARDA(2)C WD/DD genotype and 67% has the GNB3 CT/TT genotype. Besides higher baseline norepinephrine levels, the presence of both ARDA(2)C WD/DD and GNB3 CT/TT genotypes showed a positive predictive value of 82% and a negative predictive value of 79% for good clonidine response. CONCLUSIONS: These results suggest that neurohormonal and genetic testing may be used as predictive factors for the additive effects of clonidine on the diuresis and natriuresis effects of diuretics in patients with cirrhosis with refractory ascites.

Sex-specific genetic architecture of human fatness in Chinese: the SAPPHIRe Study.

To dissect the genetic architecture of sexual dimorphism in obesity-related traits, we evaluated the sex-genotype interaction, sex-specific heritability and genome-wide linkages for seven measurements related to obesity. A total of 1,365 non-diabetic Chinese subjects from the family study of the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance were used to search for quantitative trait loci (QTLs) responsible for the obesity-related traits. Pleiotropy and co-incidence effects from the QTLs were also examined using the bivariate linkage approach. We found that sex-specific differences in heritability and the genotype-sex interaction effects were substantially significant for most of these traits. Several QTLs with strong linkage evidence were identified after incorporating genotype by sex (G × S) interactions into the linkage mapping, including one QTL for hip circumference [maximum LOD score (MLS) = 4.22, empirical p = 0.000033] and two QTLs: for BMI on chromosome 12q with MLS 3.37 (empirical p = 0.0043) and 3.10 (empirical p = 0.0054). Sex-specific analyses demonstrated that these linkage signals all resulted from females rather than males. Most of these QTLs for obesity-related traits replicated the findings in other ethnic groups. Bivariate linkage analyses showed several obesity traits were influenced by a common set of QTLs. All regions with linkage signals were observed in one gender, but not in the whole sample, suggesting the genetic architecture of obesity-related traits does differ by gender. These findings are useful for further identification of the liability genes for these phenotypes through candidate genes or genome-wide association analysis.

Penrose drain tube as a guide for endostaplers during lobectomy via video-assisted thoracoscopic surgery.

Endostaplers are widely used in pulmonary lobectomy procedures performed through video-assisted thoracoscopic surgery (VATS). Using them to approach fused pulmonary fissures during VATS lobectomy procedures is safer and quicker than manual techniques. However, the direction of endostaplers is sometimes limited by the location of the working ports, which may result in difficulties in positioning the endostaplers or even traction or laceration of peripheral lung tissue. We describe here a useful surgical technique that uses a Penrose drain tube as a guide for the endostapler, making its use to divide fused pulmonary fissures during VATS lobectomy easier and safer.